NLN

Summary

NLN (neurolysin, HGNC:16058) is a protein-coding gene on chromosome 5q12.3, encoding Neurolysin, mitochondrial (Q9BYT8). Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A.

This gene encodes a member of the metallopeptidase M3 protein family that cleaves neurotensin at the Pro10-Tyr11 bond, leading to the formation of neurotensin(1-10) and neurotensin(11-13). The encoded protein is likely involved in the termination of the neurotensinergic signal in the central nervous system and in the gastrointestinal tract.

Source: NCBI Gene 57486 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 130 total
• Druggable target: yes
• MANE Select transcript: NM_020726

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16058
Approved symbol	NLN
Name	neurolysin
Location	5q12.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1226
Ensembl gene	ENSG00000123213
Ensembl biotype	protein_coding
OMIM	611530
Entrez	57486

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000380985, ENST00000502464, ENST00000506539, ENST00000506677, ENST00000506799, ENST00000507201, ENST00000509935, ENST00000511299, ENST00000514991, ENST00000515595, ENST00000865845, ENST00000865846

RefSeq mRNA: 1 — MANE Select: NM_020726 NM_020726

CCDS: CCDS3989

Canonical transcript exons

ENST00000380985 — 13 exons

Exon	Start	End
ENSE00001487107	65822781	65829283
ENSE00001487158	65722205	65722414
ENSE00003486499	65792454	65792655
ENSE00003493478	65758567	65758826
ENSE00003500732	65762960	65763108
ENSE00003540777	65777427	65777534
ENSE00003599694	65780179	65780281
ENSE00003601786	65810037	65810165
ENSE00003603358	65785775	65785910
ENSE00003662810	65812255	65812391
ENSE00003682820	65809515	65809701
ENSE00003684822	65788118	65788484
ENSE00003694419	65781261	65781421

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 92.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2834 / max 155.1186, expressed in 1795 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56694	15.4907	1794
56695	0.3201	125
56696	0.2393	91
56703	0.1561	55
56702	0.0426	26
56701	0.0347	21

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	92.01	gold quality
secondary oocyte	CL:0000655	90.58	gold quality
tibialis anterior	UBERON:0001385	90.52	gold quality
ileal mucosa	UBERON:0000331	89.60	gold quality
cortical plate	UBERON:0005343	89.50	gold quality
pancreatic ductal cell	CL:0002079	88.05	gold quality
stromal cell of endometrium	CL:0002255	86.77	gold quality
monocyte	CL:0000576	86.52	gold quality
gastrocnemius	UBERON:0001388	86.29	gold quality
muscle of leg	UBERON:0001383	86.16	gold quality
leukocyte	CL:0000738	85.76	gold quality
deltoid	UBERON:0001476	85.69	silver quality
ganglionic eminence	UBERON:0004023	85.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.02	gold quality
epithelial cell of pancreas	CL:0000083	84.48	silver quality
quadriceps femoris	UBERON:0001377	84.28	gold quality
vastus lateralis	UBERON:0001379	83.64	silver quality
Brodmann (1909) area 23	UBERON:0013554	83.53	gold quality
liver	UBERON:0002107	83.32	gold quality
islet of Langerhans	UBERON:0000006	83.30	gold quality
right lobe of liver	UBERON:0001114	82.51	gold quality
skeletal muscle tissue	UBERON:0001134	82.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.35	gold quality
muscle tissue	UBERON:0002385	82.04	gold quality
calcaneal tendon	UBERON:0003701	81.65	gold quality
middle temporal gyrus	UBERON:0002771	81.51	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.20	gold quality
rectum	UBERON:0001052	81.09	gold quality
corpus callosum	UBERON:0002336	80.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.67	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	495.16
E-ANND-3	no	6.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

208 targeting NLN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 4)

• Mutations at only two residues (Arg-470 and Arg-498) are required to swap specificity with thimet oligopeptidase, a result that is confirmed by testing the two-mutant constructs. (PMID:17251185)
• The crystal structure of human neurolysin(E475Q) in complex with the products of neurotensin cleavage at 2.7A revealed a closed conformation with an internal cavity that restricts substrate length and highlighted the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity. (PMID:29183787)
• The mitochondrial peptidase, neurolysin, regulates respiratory chain supercomplex formation and is necessary for AML viability. (PMID:32269163)
• Structural basis of divergent substrate recognition and inhibition of human neurolysin. (PMID:39117724)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nln	ENSDARG00000019233
mus_musculus	Nln	ENSMUSG00000021710
rattus_norvegicus	Nln	ENSRNOG00000011561
drosophila_melanogaster	CG11771	FBGN0039252
caenorhabditis_elegans		WBGENE00013997

Paralogs (2): MIPEP (ENSG00000027001), THOP1 (ENSG00000172009)

Protein

Protein identifiers

Neurolysin, mitochondrial — Q9BYT8 (reviewed: Q9BYT8)

Alternative names: Angiotensin-binding protein, Microsomal endopeptidase, Mitochondrial oligopeptidase M, Neurotensin endopeptidase

All UniProt accessions (5): D6R9Y0, E9PCB6, Q9BYT8, H0YAF7, H0YAK4

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1.

Subcellular location. Mitochondrion intermembrane space. Cytoplasm. Cytosol.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M3 family.

RefSeq proteins (1): NP_065777* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001567	Pept_M3A_M3B_dom	Domain
IPR024077	Neurolysin/TOP_dom2	Homologous_superfamily
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR024080	Neurolysin/TOP_N	Homologous_superfamily
IPR045090	Pept_M3A_M3B	Family

Pfam: PF01432

Enzyme classification (BRENDA):

• EC 3.4.24.16 — neurolysin (BRENDA: 9 organisms, 259 substrates, 134 inhibitors, 172 Km, 207 kcat entries)

Substrate kinetics (BRENDA)

127 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
(7-METHOXYCOUMARIN-4-YL)-ACETYL-PRO-LEU-GLY-PRO-	0.0061–0.0139	5
ABZ-GFSRFRQEDDNP	0.0008–0.0083	5
ABZ-GFSAFRQEDDNP	0.0009–0.0078	4
ABZ-GFSFFRQEDDNP	0.0015–0.0101	4
ABZ-GFSHFRQEDDNP	0.0018–0.0106	4
ABZ-GFSLFRQEDDNP	0.0018–0.0061	4
ABZ-GFSQFRQEDDNP	0.0016–0.021	4
ABZ-GFSSFRQEDDNP	0.0056–0.0111	4
ABZ-GFSWFRQEDDNP	0.0008–0.006	4
ABZ-GFSYFRQEDDNP	0.0012–0.0096	4
2-AMINOBENZOYL-GFSPFRQ-(N-2,4-DINITROPHENYL)ETHY	0.0006–0.0031	3
ABZ-GFSEFRQEDDNP	0.0024–0.0053	3
ABZ-GFSIFRQEDDNP	0.0008–0.0048	3
NEUROTENSIN	0.002–0.0029	3
(7-METHOXY-COUMARIN-4-YL)ACETYL-RPKPVE-NVA-WRK(2	6–14	2

UniProt features (68 total): helix 36, strand 11, turn 9, sequence variant 5, binding site 3, transit peptide 1, chain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8VJY	X-RAY DIFFRACTION	1.95
8VJU	X-RAY DIFFRACTION	1.99
8VJV	X-RAY DIFFRACTION	2.12
8VJW	X-RAY DIFFRACTION	2.49
5LUZ	X-RAY DIFFRACTION	2.7
5LV0	X-RAY DIFFRACTION	2.7
8VJX	X-RAY DIFFRACTION	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYT8-F1	92.87	0.86

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 498

Ligand- & substrate-binding residues (3): 497; 501; 504

Post-translational modifications (1): 664

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 193 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CELL_DIFFERENTIATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, USF_C, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (5): regulation of gluconeogenesis (GO:0006111), proteolysis (GO:0006508), peptide metabolic process (GO:0006518), G protein-coupled receptor signaling pathway (GO:0007186), regulation of skeletal muscle fiber differentiation (GO:1902809)

GO Molecular Function (6): metalloendopeptidase activity (GO:0004222), peptide binding (GO:0042277), metal ion binding (GO:0046872), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
gluconeogenesis	1
regulation of glucose metabolic process	1
regulation of carbohydrate biosynthetic process	1
protein metabolic process	1
metabolic process	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of myotube differentiation	1
skeletal muscle fiber differentiation	1
regulation of skeletal muscle cell differentiation	1
endopeptidase activity	1
metallopeptidase activity	1
binding	1
cation binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
mitochondrial envelope	1
organelle envelope lumen	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLN	NTS	P30990	855
NLN	ACE	P12821	730
NLN	KNG1	P01042	713
NLN	NTSR1	P30989	672
NLN	PREP	P48147	657
NLN	REN	P00797	601
NLN	STX6	O43752	574
NLN	AGT	P01019	514
NLN	MMEL1	Q495T6	512
NLN	IDE	P14735	510
NLN	NRDC	O43847	508
NLN	PITRM1	Q5JRX3	506
NLN	CRHR1	P34998	496
NLN	MME	P08473	489
NLN	ANPEP	P15144	488

IntAct

57 interactions, top by confidence:

A	B	Type	Score
ELP3	ELP1	psi-mi:“MI:0914”(association)	0.840
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
LDLRAP1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
CBX1	KPNA3	psi-mi:“MI:0914”(association)	0.530
SMTNL2	CCNA2	psi-mi:“MI:0914”(association)	0.530
SPACA4	GRN	psi-mi:“MI:0914”(association)	0.530
NLN	KRT8	psi-mi:“MI:0915”(physical association)	0.400
NLN	MBP	psi-mi:“MI:0915”(physical association)	0.400
GPRIN3	NLN	psi-mi:“MI:0915”(physical association)	0.400
KLC4	PUF60	psi-mi:“MI:0914”(association)	0.350
Naa11		psi-mi:“MI:0914”(association)	0.350
Tnks2	AMOTL2	psi-mi:“MI:0914”(association)	0.350
Eea1	WWP2	psi-mi:“MI:0914”(association)	0.350
ZNF526	VAMP4	psi-mi:“MI:0914”(association)	0.350
RUFY1	PKN2	psi-mi:“MI:0914”(association)	0.350
Calml3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Dicer1	ENDOD1	psi-mi:“MI:0914”(association)	0.350
Fign	MAP3K4	psi-mi:“MI:0914”(association)	0.350
Cetn2	SFI1	psi-mi:“MI:0914”(association)	0.350
GAR1	TAF1	psi-mi:“MI:0914”(association)	0.350
HIF1A	PIAS1	psi-mi:“MI:0914”(association)	0.350
RASSF8	POLR2H	psi-mi:“MI:0914”(association)	0.350
NCAPD3	SMC2	psi-mi:“MI:0914”(association)	0.350
MRPL9	MRPL43	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350

BioGRID (79): NLN (Affinity Capture-MS), SYNE1 (Co-fractionation), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS), NLN (Affinity Capture-MS)

ESM2 similar proteins: A2VDQ5, A4IG42, A6H611, A8E657, A8WFT6, A9RBS1, F4HTQ1, F4KDA5, O22190, P24155, P24527, P30349, P42675, P42676, P47788, P52888, P55786, Q01992, Q02038, Q09152, Q0VCA5, Q11011, Q1JPJ8, Q1MTD3, Q28FT4, Q32PX9, Q3T0H0, Q3V384, Q502K2, Q54DD2, Q56H28, Q5R9V6, Q5U5V2, Q6INN8, Q6P4Z6, Q6PB06, Q6S9C8, Q8BH66, Q8C1A5, Q8GWT4

Diamond homologs: A2VDQ5, F4HTQ1, P24155, P25375, P27237, P27298, P42675, P42676, P44573, P47788, P52888, Q02038, Q1JPJ8, Q54DD2, Q5R9V6, Q8C1A5, Q91YP2, Q9BYT8, P24171, P27236, Q949P2, Q94AM1, Q5RF14, Q99797

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

130 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2453 predictions. Top by Δscore:

Variant	Effect	Δscore
5:65758565:A:AG	acceptor_gain	1.0000
5:65758566:G:GG	acceptor_gain	1.0000
5:65758566:GA:G	acceptor_gain	1.0000
5:65758566:GAGTT:G	acceptor_gain	1.0000
5:65758769:G:GT	donor_gain	1.0000
5:65758769:G:T	donor_gain	1.0000
5:65758809:TAG:T	donor_gain	1.0000
5:65758810:AGA:A	donor_gain	1.0000
5:65758814:G:GG	donor_gain	1.0000
5:65762958:A:AG	acceptor_gain	1.0000
5:65762958:AGT:A	acceptor_gain	1.0000
5:65762958:AGTG:A	acceptor_gain	1.0000
5:65762959:G:GA	acceptor_gain	1.0000
5:65762959:GT:G	acceptor_gain	1.0000
5:65762959:GTG:G	acceptor_gain	1.0000
5:65762959:GTGG:G	acceptor_gain	1.0000
5:65762959:GTGGA:G	acceptor_gain	1.0000
5:65777425:AG:A	acceptor_gain	1.0000
5:65777426:GG:G	acceptor_gain	1.0000
5:65777530:AGAAT:A	donor_gain	1.0000
5:65777531:GAAT:G	donor_gain	1.0000
5:65777531:GAATG:G	donor_gain	1.0000
5:65777532:AAT:A	donor_gain	1.0000
5:65777533:AT:A	donor_gain	1.0000
5:65777534:TG:T	donor_loss	1.0000
5:65777535:G:GG	donor_gain	1.0000
5:65777536:TGAGT:T	donor_loss	1.0000
5:65780175:TCA:T	acceptor_loss	1.0000
5:65780177:A:AG	acceptor_gain	1.0000
5:65780177:A:T	acceptor_loss	1.0000

AlphaMissense

4670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:65792631:C:A	H501Q	0.999
5:65792631:C:G	H501Q	0.999
5:65763014:G:C	R119P	0.998
5:65763022:A:C	S122R	0.998
5:65763024:T:A	S122R	0.998
5:65763024:T:G	S122R	0.998
5:65763031:G:C	A125P	0.998
5:65788399:T:A	W414R	0.998
5:65788399:T:C	W414R	0.998
5:65792629:C:G	H501D	0.998
5:65781382:A:C	R261S	0.997
5:65781382:A:T	R261S	0.997
5:65788401:G:C	W414C	0.997
5:65788401:G:T	W414C	0.997
5:65792617:C:G	H497D	0.997
5:65792621:A:T	E498V	0.997
5:65810066:A:C	S582R	0.997
5:65810068:C:A	S582R	0.997
5:65810068:C:G	S582R	0.997
5:65822809:T:C	L670P	0.997
5:65763044:T:C	L129P	0.996
5:65781381:G:C	R261T	0.996
5:65788457:G:A	G433E	0.996
5:65792540:C:A	A471D	0.996
5:65792622:G:C	E498D	0.996
5:65792622:G:T	E498D	0.996
5:65792627:G:A	G500D	0.996
5:65792630:A:C	H501P	0.996
5:65822793:T:G	Y665D	0.996
5:65758673:T:A	W50R	0.995

dbSNP variants (sampled 300 via entrez): RS1000005800 (5:65825525 GT>G), RS1000026857 (5:65736606 A>G), RS1000058191 (5:65825914 A>G), RS1000097906 (5:65740361 T>C), RS1000124969 (5:65809808 C>A,T), RS1000136127 (5:65745111 A>T), RS1000148303 (5:65764653 G>C,T), RS1000195967 (5:65768010 A>G), RS1000231448 (5:65789808 T>A), RS1000237684 (5:65762675 C>A), RS1000256876 (5:65783512 G>A,C), RS1000277919 (5:65742833 A>G,T), RS1000322220 (5:65803361 C>T), RS1000326691 (5:65808120 A>G), RS1000380114 (5:65749095 C>A,T)

Disease associations

OMIM: gene MIM:611530 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002685_2	Refractive astigmatism	2.000000e-06
GCST004069_14	Cerebrospinal fluid AB1-42 levels	6.000000e-07
GCST007000_2	Logical memory (delayed recall) in mild cognitive impairment	8.000000e-07
GCST010701_121	Cortical surface area (MOSTest)	6.000000e-11
GCST010702_62	Subcortical volume (MOSTest)	6.000000e-12
GCST010703_77	Brain morphology (MOSTest)	2.000000e-16
GCST012316_6	ghrelin levels	2.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004874	memory performance
EFO:0004346	neuroimaging measurement
EFO:0600001	ghrelin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465352 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

17 potent at pChembl≥5 of 22 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.97	Kd	107.2	nM	CHEMBL5653589
6.79	ED50	163.8	nM	CHEMBL5653589
5.70	EC50	2000	nM	CHEMBL5426568
5.54	EC50	2900	nM	CHEMBL5423569
5.47	EC50	3400	nM	CHEMBL5414219
5.44	EC50	3600	nM	CHEMBL5415307
5.42	EC50	3800	nM	CHEMBL5440102
5.39	EC50	4100	nM	CHEMBL5394053
5.37	EC50	4300	nM	CHEMBL5410608
5.36	EC50	4400	nM	CHEMBL5084793
5.28	EC50	5200	nM	CHEMBL5429733
5.27	EC50	5400	nM	CHEMBL5406111
5.27	EC50	5400	nM	CHEMBL5085279
5.26	EC50	5500	nM	CHEMBL5420766
5.20	EC50	6300	nM	CHEMBL5415776
5.17	EC50	6800	nM	CHEMBL5436327
5.16	EC50	7000	nM	CHEMBL5398045

PubChem BioAssay actives

16 with measured affinity, of 49 total; 16 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148872: Binding affinity to human NLN incubated for 45 mins by Kinobead based pull down assay	kd	0.1072	uM
(1R)-1-[5-(4-chlorophenyl)-1H-imidazol-2-yl]-2-(1H-imidazol-5-yl)ethanamine	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	2.0000	uM
(1S)-1-[5-(4-chlorophenyl)-1H-imidazol-2-yl]-2-(1H-imidazol-5-yl)ethanamine	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	2.9000	uM
(2S)-2-amino-3-(1H-imidazol-5-yl)-N-(naphthalen-1-ylmethyl)propanethioamide	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	3.4000	uM
(2R)-2-amino-3-(1H-imidazol-5-yl)-N-methyl-N-(naphthalen-1-ylmethyl)propanamide	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	3.6000	uM
(2S)-2-amino-3-(1H-imidazol-5-yl)-N-methyl-N-(naphthalen-1-ylmethyl)propanamide	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	3.8000	uM
(1S)-2-(1H-imidazol-5-yl)-1-(5-naphthalen-1-yl-1H-imidazol-2-yl)ethanamine	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	4.1000	uM
(2S)-2-amino-1-[4-[(2-fluorophenyl)methyl]piperidin-1-yl]-3-(1H-imidazol-5-yl)propan-1-one	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	4.3000	uM
(2S)-2-amino-3-(1H-imidazol-5-yl)-N-(naphthalen-2-ylmethyl)propanamide	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	4.4000	uM
(2S)-2-amino-N-benzyl-3-(1H-imidazol-5-yl)-N-[2-(1H-indol-3-yl)ethyl]propanamide	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	5.2000	uM
(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenyl-N-(2-phenylethyl)propanamide	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	5.4000	uM
(2R)-2-amino-1-[4-[(2-fluorophenyl)methyl]piperidin-1-yl]-3-(1H-imidazol-5-yl)propan-1-one	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	5.4000	uM
(1S)-2-(1H-imidazol-5-yl)-1-(5-naphthalen-2-yl-1H-imidazol-2-yl)ethanamine	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	5.5000	uM
(2S)-2-amino-3-(1H-imidazol-5-yl)-N-[2-(1H-indol-3-yl)ethyl]propanamide	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	6.3000	uM
(1R)-2-(1H-imidazol-5-yl)-1-(5-naphthalen-2-yl-1H-imidazol-2-yl)ethanamine	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	6.8000	uM
(2S)-2-amino-3-(1H-imidazol-5-yl)-N-quinolin-8-ylpropanamide	1985704: Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	ec50	7.0000	uM

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	6
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Arsenic	increases expression, decreases methylation, increases abundance, affects cotreatment	2
Nickel	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
4-phenylbutyric acid	decreases expression	1
K 7174	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338497	Binding	Activation of Nln (unknown origin) using Mca-Pro-Leu-Gly-Pro-D-Lys(DNP)- OH as substrate preincubated for 10 mins followed by substrate addition measured for 20 mins by fluorescence based assay	Imidazole Bioisostere Activators of Endopeptidase Neurolysin with Enhanced Potency and Metabolic Stability. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9LC	Ubigene HEK293 NLN KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.